The goal of this Program Project application is to assign structure and function to the protein products of genomic open reading frames for which there are no homologues with known three dimensional structure and function. In a departure from current practice, the applicant and his project leaders are proposing to mount a comprehensive, concerted effort, using high throughput crystallographic approaches, to determine protein function from atomic level structure. Complementary DNA from selected Hemophilus influenzae genes, and other microorganisms as indicated, will be cloned for expression in Escherichia coli and purification of the protein products in order to obtain sufficient quantities of protein for crystallization and X-ray crystallographic and NMR 3D structure determinations.